Chemical methods will be developed for the preparation of six classes of C-nucleoside derivatives which are close analogs of either synthetic derivatives with established antitumor and/or antiviral activity or natural products. Isosteres and isoelectronic analogs of nicotinamide nucleoside (classes 1 and 2) will by synthesized. These C-nucleosides may show potent antitumor activity by inhibiting IMP-dehydrogenase or they may potentiate the activity of other anticancer drugs whose mode of action involves DNA strand disruption. NAD analogs (class 3) in which the nicotinamide nucleoside is replaced by a class 1 or class 2 C-nucleoside will be prepared. These analogs may be more active that the C-nucleosides of classes 1 and 2. C-Nucleoside analogs (class 4) of the potent antiherpetic and potential antileukemic agents, FMAU and FEAU, will be synthesized by modification of a preformed nucleoside (gamma-uridine) at the sugar moiety. Novel ring transformation reactions will be developed and applied to facile synthesis of antitumor antibiotics, showdomycin and oxazinomycin, and their analogs (classes 5 and 6) from Gamma-uridine. "In house" biochemical and chemotherapeutic collaborative studies for proper evaluation of the targeted C-nucleosides are described briefly. From these studies, structure-activity relationships should be forthcoming to aid in the development of new agents superior to those currently available for the treatment of cancer and/or viral infection in man.